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Alzheimer’s disease is a progressive condition that affects areas of the brain involved in memory, cognition, judgment, language and behavior. It is the most common dementia among older adults. In the United States, more than 4 million people suffer from Alzheimer’s disease, with that number expected to grow to 14 million by 2050. Five drugs—with combined sales of approximately $5 billion—are approved in the U.S. to treat Alzheimer’s disease. However, they treat symptoms with only modest effect, and none modify the underlying disease. This underscores the significant unmet medical need in Alzheimer’s disease.
Results of the first pivotal clinical trial of Dimebon in Alzheimer’s disease, published in the July 19, 2008 issue of The Lancet, showed that Dimebon improved the clinical course of Alzheimer’s disease. In this randomized, double-blind, placebo-controlled trial of 183 patients with mild-to-moderate Alzheimer’s disease, patients treated with Dimebon experienced statistically significant improvements compared to placebo in all the key aspects of the disease: memory and thinking, activities of daily living, behavior and overall function. After both six months and a full year of treatment, Dimebon-treated patients were significantly better than placebo-treated patients on all key aspects of the disease. The benefit on the primary endpoint, the ADAS-cog at six months, was particularly robust (p<0.0001). Patients treated with Dimebon were also significantly improved at six months over baseline on all measures (p=0.005 on ADAS-cog). Dimebon benefit over placebo continued to increase throughout the 12-month treatment period. At the end of 12 months, Dimebon-treated patients preserved their starting level of function on each measure of Alzheimer’s disease.
Dimebon was well-tolerated throughout the trial. There was no difference between the Dimebon and placebo groups in the number of patients with adverse events, and the most common side effects seen were dry mouth (18 percent versus 1 percent for placebo) and depressed mood/depression (15 percent versus 5 percent for placebo). Importantly, fewer patients treated with Dimebon had serious adverse events than did patients on placebo at the end of the study (3 percent versus 12 percent; p=0.03).
Additional analyses of the Dimebon pivotal study data presented at recent medical conferences showed that Dimebon’s impact extended to caregivers. Behavioral improvements in Dimebon-treated patients resulted in a significant decrease in caregiver distress at six months and at one year compared to the distress of caregivers of placebo-treated patients. Further, after six months, caregivers of Dimebon-treated patients saved approximately one hour per day assisting patients with activities of daily living compared to caregivers of placebo-treated patients.
The Dimebon pivotal clinical study is the first Alzheimer’s disease study in which a drug has achieved statistically significant benefits of this breadth, size and duration in a one year, well-controlled trial.
In January 2008, the U.S. Food and Drug Administration (FDA) informed us that this trial can be used as one of the two pivotal studies required to support the approval of Dimebon to treat mild-to-moderate Alzheimer’s disease, as long as a significant portion of the sites in our confirmatory pivotal Phase 3 trial are located in the United States. However, as is typically the case at this stage of the regulatory review process, the FDA has not yet performed an in-depth review of our preclinical and clinical data, so its views remain subject to change.
We initiated our confirmatory pivotal Phase 3 Alzheimer’s disease trial in the second quarter of 2008.
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